Compound Action Potential Thresholds Research Articles

Prediction of Cochlear Implant Fitting by Machine Learning Techniques.

This study aimed to evaluate the differences in electrically evoked compound action potential (ECAP) thresholds and postoperative mapping current (T) levels between electrode types after cochlear implantation, the correlation between ECAP thresholds and T levels, and the performance of machine learning techniques in predicting postoperative T levels. Retrospective case review. Tertiary hospital. We reviewed the charts of 124 ears of children with severe-to-profound hearing loss who had undergone cochlear implantation. We compared ECAP thresholds and T levels from different electrodes, calculated correlations between ECAP thresholds and T levels, and created five prediction models of T levels at switch-on and 6 months after surgery. The accuracy of prediction in postoperative mapping current (T) levels. The ECAP thresholds of the slim modiolar electrodes were significantly lower than those of the straight electrodes on the apical side. However, there was no significant difference in the neural response telemetry thresholds between the two electrodes on the basal side. Lasso regression achieved the most accurate prediction of T levels at switch-on, and the random forest algorithm achieved the most accurate prediction of T levels 6 months after surgery in this dataset. Machine learning techniques could be useful for accurately predicting postoperative T levels after cochlear implantation in children.

Cochlear Implant Outcomes in Patients With TMTC2-Associated Sensorineural Hearing Loss and Auditory Neuropathy/Auditory Dys-Synchrony.

To investigate the outcomes of cochlear implantation in patients with TMTC2-associated sensorineural hearing loss and auditory neuropathy/auditory dys-synchrony. Adult and pediatric cochlear implant (CI) patients followed in an academic center who tested positive for TMTC2 genetic variant rs35725509. Cochlear implantation. Speech perception scores in quiet. Ten CI patients were identified with TMTC2 variant rs35725509 out of 157 patients who underwent genetic testing (i.e., 6.3% of patients tested). All demonstrated progressive, bilateral hearing loss with severe-to-profound audiometric thresholds preoperatively. Pre-CI and 1-year post-CI speech recognition percent correct scores were compared. Post-CI speech perception (mean 61.0%, standard deviation 31.4%) was significantly higher than pre-CI speech perception (mean 21.0%, standard deviation 27.0%) (p = 0.002). Individually, 9 of the 10 subjects experienced significant improvements in speech perception pre- to post-CI (p < 0.05). Electrically evoked compound action potential measures were available for five patients, and all showed normal electrically evoked compound action potential thresholds. Patients with TMTC2-associated sensorineural hearing loss and auditory neuropathy/auditory dys-synchrony have significantly improved speech perception outcomes with cochlear implantation and should be considered candidates for this intervention if there are no other contraindications.

The Effect of Electrode Position on Behavioral and Electrophysiologic Measurements in Perimodiolar Cochlear Implants.

The shape and position of cochlear implant electrodes could potentially influence speech perception, as this determines the proximity of implant electrodes to the spiral ganglion. However, the literature to date reveals no consistent association between speech perception and either the proximity of electrode to the medial cochlear wall or the depth of insertion. These relationships were explored in a group of implant recipients receiving the same precurved electrode. This was a retrospective study of adults who underwent cochlear implantation with Cochlear Ltd.'s Slim Perimodiolar electrode at the Royal Victorian Eye and Ear Hospital between 2015 and 2018 (n = 52). Postoperative images were obtained using cone beam computed tomography (CBCT) and analyzed by multi-planar reconstruction to identify the position of the electrode contacts within the cochlea, including estimates of the proximity of the electrodes to the medial cochlear wall or modiolus and the angular depth of insertion. Consonant-vowel-consonant (CVC) monosyllabic phonemes were determined preoperatively, and at 3 and 12 months postoperatively. Electrically evoked compound action potential (ECAP) thresholds and impedance were measured from the implant array immediately after implantation. The relationships between electrode position and speech perception, electrode impedance, and ECAP threshold were an analyzed by Pearson correlation. Age had a negative impact on speech perception at 3 months but not 12 months. None of the electrode-wide measures of proximity between electrode contacts and the modiolus, nor measures of proximity to the medial cochlear wall, nor the angular depth of insertion of the most apical electrode correlated with speech perception. However, there was a moderate correlation between speech perception and the position of the most basal electrode contacts; poorer speech perception was associated with a greater distance to the modiolus. ECAP thresholds were inversely related to the distance between electrode contacts and the modiolus, but there was no clear association between this distance and impedance. Speech perception was significantly affected by the proximity of the most basal electrodes to the modiolus, suggesting that positioning of these electrodes may be important for optimizing speech perception. ECAP thresholds might provide an indication of this proximity, allowing for its optimization during surgery.

Measurements of bone-conducted sound in the chinchilla external ear

We measure bone-conduction (BC) induced skull velocity, sound pressure at the tympanic membrane (TM) and inner-ear compound-action potentials (CAP) before and after manipulating the ear canal, ossicles, and the jaw to investigate the generation of BC induced ear-canal sound pressures and their contribution to inner-ear BC response in the ears of chinchillas. These measurements suggest that in chinchilla: i.) Vibrations of the bony ear canal walls contribute significantly to BC-induced ear canal sound pressures, as occluding the ear canal at the bone-cartilaginous border causes a 10 dB increase in sound pressure at the TM (PTM) at frequencies below 2 kHz. ii.) The contributions to PTM of ossicular and TM motions when driven in reverse by BC-induced inner-ear sound pressures are small. iii.) The contribution of relative motions of the jaw and ear canal to PTM is small. iv.) Comparison of the effect of canal occlusion on PTM and CAP thresholds point out that BC-induced ear canal sound pressures contribute significantly to bone-conduction stimulation of the inner ear when the ear canal is occluded.

Features of processor fitting in patients with different types of cochlear implant electrode array

Introduction. The results of cochlear implantation in patients with bilateral sensorineural hearing loss are influenced by many factors, including the type of electrode array. The location of the electrodes in relation to neurons of spiral ganglion affects on levels of perception of the patient's hearing sensations.Aim. To evaluate the dependence of electrically evoked compound action potential (ECAP) thresholds values and comfortable levels depends on electrode array type.Materials and methods. 26 patients with bilateral sensorineural hearing loss with cochlear implantation systems were examined. The patients were divided into 2 groups: 1) patients with a straight electrode array (n = 14); 2) patients with a perimodiolar electrode array (n = 12). We tested speech intelligibility and ECAP thresholds. The difference in the values of both parameters was estimated.Results. For both groups of patients, the relationship between the threshold's profiles of ECAP thresholds and maximum comfortable stimulation levels was detected. For patients from the first group (straight electrode array), the differences in values between the studied parameters were 30.6 ± 6.1%. In patients from the second group, the differences in the values of the thresholds for ECAP thresholds and the levels of comfortable stimulation ranged 2.4 ± 2.1%.Conclusion. The perimodiolar electrode array is located closer to the neurons of the spiral ganglion, which may explain the greater relationship between the values of the ECAP thresholds and the levels of comfortable stimulation. This pattern must be considered when programming the processor of the cochlear implantation system.

Physiologic Effects of Microneedle-Mediated Intracochlear Dexamethasone Injection in the Guinea Pig.

Oral or intratympanic corticosteroids are commonly used to treat sudden sensorineural hearing loss (SSHL), tinnitus, and Meniere disease. Direct intracochlear delivery has been proposed to overcome the variability in bioavailability and efficacy of systemic or middle ear delivery. In this study, we aim to characterize the physiologic consequences of microneedle-mediated direct intracochlear injection of dexamethasone through the round window membrane (RWM). In Hartley guinea pigs (n = 5), a post-auricular incision followed by bullostomy was made to access the round window membrane. Using 100 μm diameter hollow microneedles, 1.0 μl of 10 mg/ml dexamethasone was injected through the RWM over 1 min. Compound action potential (CAP) and distortion product otoacoustic action emissions (DPOAE) were measured before perforation, at 1 h, and at 5 h following injection. CAP hearing thresholds were measured from 0.5 to 40 kHz, and DPOAE f2 frequencies ranged from 1.0 and 32 kHz. Repeated measures ANOVA followed by pairwise t-tests were used for statistical analysis. ANOVA identified significant CAP threshold shifts at four frequencies (4, 16, 36, and 40 kHz) and differences in DPOAE at 1 frequency (6 kHz). Paired t-tests revealed differences between the pre-perforation and 1 h time point. By 5 h post injection, both CAP hearing thresholds and DPOAE recover and are not significantly different from baseline thresholds. Direct intracochlear delivery of dexamethasone via microneedles results in temporary shifts in hearing thresholds that resolve by 5 hours, thus supporting microneedle technology for the treatment of inner ear disorders. NA Laryngoscope, 134:388-392, 2024.

Audiogram Configuration, Molecular Etiology, and Outcome of Cochlear Implantation in Postlingual Auditory Neuropathy Spectrum Disorder.

To explore the diverse molecular etiologies of postlingual auditory neuropathy spectrum disorder (ANSD) and report on the electrically evoked compound action potential (ECAP) thresholds and the outcome of cochlear implantation (CI). Patients with late-onset, progressive hearing loss who went through molecular genetic testing were enrolled. Type of sensorineural hearing loss (SNHL) was classified as flat, reverse-slope, midfrequency, downsloping, or ski slope. We identified postlingual ANSD subjects through diagnostic tracts applied differently depending on the degree of SNHL. For CI recipients, individual ECAP thresholds, postoperative speech perception abilities, and the genetic cause were analyzed. The detection rate of ANSD among patients with postlingual SNHL was 5.1% (15/293 probands). Diverse genetic etiologies were identified in 7 (46.6%) of the 15 postlingual ANSD subjects, the genetic cause being found exclusively in subjects with reverse-slope SNHL. The pattern of intraoperative ECAP responses was also diverse and showed some correlation with the genetic etiology. Despite the diverse molecular etiology and ECAP responses, CI in postlingual ANSD patients, including those with features involving the postsynaptic component, yielded significant improvements in speech understanding. This study proposes a differentiated diagnostic approach that focuses on both poor speech discrimination and reverse-slope hearing loss for the diagnosis of ANSD. Based on the improvement of speech understanding from all cochlear implantees with ANSD as well as the correlation between the genetic etiology and ECAP thresholds, we suggest that CI can significantly benefit ANSD subjects even those with unknown etiologies unless there is overt peripheral neuropathy.

Short-term overstimulation affects peripheral but not central excitability in an animal model of cochlear implantation

Objective: Upper current limits (C-levels) are sometimes extremely increased over time since this procedure can enhance speech perception. It should be clarified if a larger amount of electrical stimulation is tolerated by the remaining peripheral and central auditory pathway. Materials and Methods: An animal electrode array was inserted in mechanically deafened guinea pigs. C-levels were adjusted to a mean of approximately 10 CL (‘LOS' group), 40 CL (‘MOS' group) or 60 CL (‘HOS’ group) above the electrode specific electrically evoked compound action potential (eCAP) threshold. The stimulation was performed via a sound processor in standardized auditory environment. Implanted and not stimulated animals served as controls. Results: A significant eCAP threshold shift was observed in the ‘HOS’-group aftereight hours of stimulation at basal electrodes. Electrically evoked auditory brainstem thresholds were stable over time in all stimulation groups. The ratio between eCAP- and eABR threshold shifts was significantly enhanced in the ‘HOS’- group. Conclusion: Even short-time overstimulation reduces the excitability of peripheral but not central auditory structures. The changed relationship between the excitability of spiral ganglion neurons and inferior colliculus neurons seems to indicate an overstimulation. The results are of utmost importance for a safe CI-processor fitting especially in children or non-compliant patients

Relationship between electrically evoked compound action potential thresholds and behavioral T-levels in implanted children with cochlear nerve deficiency

It is challenging to program children with cochlear nerve deficiency (CND) due to limited auditory and speech abilities or concurrent neurological deficits. Electrically evoked compound action potential (ECAP) thresholds have been widely used by many audiologists to help cochlear implant programming for children who cannot cooperate with behavioral testing. However, the relationship between ECAP thresholds and behavioral levels of cochlear nerve in children with CND remains unclear. This study aimed to investigate how well ECAP thresholds are related to behavioral thresholds in the MAP for children with CND. This study included 29 children with CND who underwent cochlear implantation. For each participant, ECAP thresholds and behavioral T-levels were measured at three electrode locations across the electrode array post-activation. The relationship between ECAP thresholds and behavioral T-levels was analyzed using Pearson’s correlation coefficient. The results showed that ECAP thresholds were significantly correlated with behavioral T-levels at the basal, middle, and apical electrodes. ECAP thresholds were equal to or higher than the behavioral T-levels for all tested electrodes, and fell within MAP’s dynamic range for approximately 90% of the tested electrodes. Moreover, the contour of the ECAP thresholds was similar to the contour of T-levels across electrodes for most participants. ECAP thresholds can help audiologists select stimulation levels more efficiently for children with CND who cannot provide sufficient behavioral response.

Acute effects of cochleostomy and electrode-array insertion on compound action potentials in normal-hearing guinea pigs.

Electrocochleography (ECochG) is increasingly used in cochlear implant (CI) surgery, in order to monitor the effect of insertion of the electrode array aiming to preserve residual hearing. However, obtained results are often difficult to interpret. Here we aim to relate changes in ECochG responses to acute trauma induced by different stages of cochlear implantation by performing ECochG at multiple time points during the procedure in normal-hearing guinea pigs. Eleven normal-hearing guinea pigs received a gold-ball electrode that was fixed in the round-window niche. ECochG recordings were performed during the four steps of cochlear implantation using the gold-ball electrode: (1) Bullostomy to expose the round window, (2) hand-drilling of 0.5-0.6 mm cochleostomy in the basal turn near the round window, (3) insertion of a short flexible electrode array, and (4) withdrawal of electrode array. Acoustical stimuli were tones varying in frequency (0.25-16 kHz) and sound level. The ECochG signal was primarily analyzed in terms of threshold, amplitude, and latency of the compound action potential (CAP). Midmodiolar sections of the implanted cochleas were analyzed in terms of trauma to hair cells, modiolar wall, osseous spiral lamina (OSL) and lateral wall. Animals were assigned to cochlear trauma categories: minimal (n = 3), moderate (n = 5), or severe (n = 3). After cochleostomy and array insertion, CAP threshold shifts increased with trauma severity. At each stage a threshold shift at high frequencies (4-16 kHz) was accompanied with a threshold shift at low frequencies (0.25-2 kHz) that was 10-20 dB smaller. Withdrawal of the array led to a further worsening of responses, which probably indicates that insertion and removal trauma affected the responses rather than the mere presence of the array. In two instances, CAP threshold shifts were considerably larger than threshold shifts of cochlear microphonics, which could be explained by neural damage due to OSL fracture. A change in amplitudes at high sound levels was strongly correlated with threshold shifts, which is relevant for clinical ECochG performed at one sound level. Basal trauma caused by cochleostomy and/or array insertion should be minimized in order to preserve the low-frequency residual hearing of CI recipients.

Comparison Between the Effect of Intra-Scalar Methylprednisolone and Sodium Hyaluronate in Impedance and Electrically Evoked Compound Action Potentials in Cochlear Implant Patients.

To evaluate and compare the effect of intra-scalar methylprednisolone and sodium hyaluronate on cochlear implants' impedance and electrically evoked compound action potentials thresholds. In a prospective randomized clinical trial, 103 children with pre-lingual hearing loss candidates for cochlear implantation at a tertiary hospital were divided into three groups based on intervention. Intraoperatively, one group received intra-scalar methylprednisolone, the second sodium hyaluronate, and the third group was the control group. Impedance and electrically evoked compound action potentials (e-ECAP) thresholds on long-term follow-up were evaluated and compared in these three groups. Significant decrease in impedance and e-ECAP thresholds were observed in all groups in a 4-year follow-up. No statistically significant difference was observed among all mentioned groups. Impedance and e-ECAP thresholds decrease in the long term, and using topical intra-scalar Healon or methylprednisolone may not significantly affect these parameters.

The intraoperative relationship between intracochlear electrical field and excitability of the auditory nerve

A limiting factor of cochlear implant (CI) technology is the electrode-contact overlapping spread of the electrode-generated intracochlear electrical field (EF). While the extent of the spread can be reduced with intracochlear ground electrodes, the stimulation level must be increased to reach similar loudness as with monopolar stimulation utilizing an extracochlear ground. In this study, we investigated the relationship between the monopolar intracochlear EF and the minimum stimulation level required for a measurable neural response assessed with electrically evoked compound action potential (eCAP) thresholds in intraoperative settings. Also, the effect of cochlear diameter on the intracochlear EF was evaluated, as narrower intracochlear EFs were found from larger than smaller cochleae in an earlier study.A total of 171 ears of severely-to-profoundly hearing-impaired patients (ages 0.7–89 years; 42.5 ± 27.8 years, mean ± SD) implanted with a Cochlear Nucleus CI522 or CI622 implant and Slim Straight electrode array or with a Med-El Synchrony implant and Flex 28 electrode array were included in the study. Normal anatomy was established and cochlear diameter was measured for all patients from preoperative imaging. Intraoperative intracochlear EF and eCAP threshold measurements were measured for both Cochlear and Med-El devices with the CIs’ back-telemetry options, and EF and eCAP were compared for Cochlear devices.The peak and width of the intracochlear EF correlated with each other (r = 0.46, p < 0.001), and both had an inverse relationship with eCAP thresholds (r = –0.41, p < 0.001 and r = –0.29, p < 0.001, respectively). The peak amplitudes of the intracochlear EF increased towards the apical part of the electrode array with both Cochlear (r = 0.97, p < 0.001) and Med-El (r = 0.80, p = 0.002) devices. The peak amplitudes of the intracochlear EF were shallower across the electrode array in large than in small cochleae (p < 0.05).Our results indicate that the responsiveness of the cochlear nerve is not only dependent on neural health but is also affected by the physical environment of the electrode array, which can be assessed by measuring the intracochlear EF. Further studies are warranted to investigate the detailed characteristics of the intracochlear current spread in CI recipients with varying anatomical features of the cochlea and with electrode arrays with different locations in the scalae or related to the modiolus in the cochleae.

Using evoked compound action potentials to quantify differential neural activation with burst and conventional, 40 Hz spinal cord stimulation in ovines.

We implanted 7 sheep with a dorsal stimulation lead at T9/T10, a dorsal ECAP sensing lead at T6/T7, and a lead also at T9/T10 but adjacent to the anterolateral system (ALS). Both burst and conventional SCS with stimulation amplitudes up to the visual motor threshold (vMT) were delivered to 3 different dorsal spinal locations, and ECAP thresholds (ECAPTs) were calculated for all combinations. Then, changes in ALS activation were assessed with both types of SCS. Evoked compound action potential thresholds and vMTs were significantly higher (P < 0.05) with conventional vs burst SCS, with no statistical difference (P > 0.05) among stimulation sites. However, the vMT-ECAPT window (a proxy for the useable therapeutic dosing range) was significantly wider (P < 0.05) with conventional vs burst SCS. No significant difference (P > 0.05) in ALS activation was noted between conventional and burst SCS. When dosed equivalently, no differentially unique change in ALS activation results with burst SCS vs conventional SCS; in addition, sub-ECAPT burst SCS results in no discernable excitability changes in the neural pathways feeding pain relevant supraspinal sites.

Single-incision cochlear implantation and hearing evaluation in piglets and minipigs

ObjectivesVarious animal models have been established and applied in hearing research. In the exploration of novel cochlear implant developments, mainly rodents have been used. Despite their important contribution to the understanding of auditory function, translation of experimental observations from rodents to humans is limited due to the size differences and genetic variability. Large animal models with better representation of the human cochlea are sparse. For this reason, we evaluated domestic piglets and Aachen minipigs for the suitability as a cochlear implantation animal model with commercially available cochlear implants. MethodsFour domestic piglets (two male and two female) and six Aachen minipigs were implanted with either MED-EL Flex24 or Flex20 cochlear implants respectively, after a step-by-step surgical approach was trained with pig cadavers. Electrophysiological measurements were performed before, during and after implantation for as long as 56 days after surgery. Auditory brainstem responses, electrocochleography as well as electrically and acoustically evoked compound action potentials were recorded. Selected cochleae were further analyzed histologically or with micro-CT imaging. ResultsA surgical approach was established using a retroauricular single incision. Baseline auditory thresholds were 27 ± 3 dB sound pressure level (SPL; auditory brainstem click responses, mean ± standard error of the mean) and ranged between 30 and 80 dB SPL in frequency-specific responses (0.5 – 32 kHz). Follow-up measurements revealed deafness within the first two weeks after surgery, but some animals partially recovered to a hearing threshold of 80 dB SPL in certain frequencies as well as in click responses. Electrically evoked compound action potential thresholds increased within the first week after surgery, which led to lower stimulation responses or increase of necessary charge input. Immune reactions and consecutive scalar fibrosis following implantation were confirmed with histological analysis of implanted cochleae and may result in increased impedances. A three-dimensional minipig micro-CT segmentation revealed cochlear volumetric data similar to human inner ear dimensions. ConclusionsThis study underlines the feasibility of cochlear implantation with clinically used cochlear implants in a large animal model with representative inner ear dimensions comparable to humans. To bridge the gap between small animal models and humans in translational research and to account for the structural and size differences, we recommend the minipig as a valuable animal model for hearing research. First insights into the induced trauma in minipigs after cochlear implant surgery and a partial hearing recovery present important data of the cochlear health changes in large animal cochleae.

Spinal Evoked Compound Action Potentials in Rats With Clinically Relevant Stimulation Modalities

ObjectivesRats are commonly used for translational pain and spinal cord stimulation (SCS) research. Although many SCS parameters are configured identically between rats and humans, stimulation amplitudes in rats are often programmed relative to visual motor threshold (vMT). Alternatively, amplitudes may be programmed relative to evoked compound action potential (ECAP) thresholds (ECAPTs), a sensed measure of neural activation. The objective of this study was to characterize ECAPTs, evoked compound muscle action potential thresholds (ECMAPTs), and vMTs with clinically relevant SCS modalities. Materials and MethodsWe implanted ten anesthetized rats with two quadripolar epidural SCS leads: one for stimulating in the lumbar spine, and another for sensing ECAPs in the thoracic spine. We then delivered two SCS paradigms to the rats. The first used 50-Hz SCS with 50-, 100-, 150-, and 200-μs pulse widths (PWs), whereas the second used a 50-Hz, 150-μs PW low-rate program (LRP) multiplexed to a 1200-Hz, 50-μs PW high-rate program (HRP). We increased SCS amplitudes up to the vMT in the first paradigm, and in the second, we increased HRP amplitudes up to the HRP ECAPT with a fixed amplitude (70% of the vMT) LRP. For each test case, we captured ECAPTs, ECMAPTs, and vMTs from each rat. ResultsvMTs were 3.0 ± 0.7 times greater than ECAPTs, with vMTs marginally (3.0 ± 3.6%) greater than ECMAPTs (mean ± SD) across all PWs with the first paradigm. With the second paradigm, we noted a negligible increase (3.6 ± 6.2%) on the LRP ECAP as HRP amplitudes were increased. ConclusionsOur results demonstrate reasonable levels of neural activation in anesthetized rats with SCS amplitudes appropriately programmed relative to vMT or ECMAPT when using clinically relevant SCS modalities. Furthermore, we demonstrate the feasibility of ECAP recording in rats with multiplexed HRP SCS.

Spironolactone Ameliorates Cochlear Implant Induced Endolymphatic Hydrops.

Endolymphatic hydrops (EH) has been observed in both animal and human cochleae following cochlear implant (CI) surgery. We tested whether EH could be eliminated by administration of mineralocorticoid steroid antagonist spironolactone and explored the electrophysiological consequences of this. Sixty-four adult guinea pigs underwent cochlear implantation with a dummy electrode. Animals then survived either 2, 7, or 28 days. Auditory function was monitored by recording electrocochleography from the round window membrane preimplantation, and on the last day of the experiment. Spironolactone or control solution was added to animals' feed for 7 days (if they survived that long) beginning immediately prior to surgery. The presence of EH was determined using thin-sheet laser imaging microscopy. Treatment with spironolactone resulted in significant reduction in EH in the second cochlear turn 7 days postimplantation. In all animals, the compound action potential (CAP) threshold was elevated 2 days postimplantation, but for most frequencies had recovered substantially by 28 days. There was no treatment effect on CAP thresholds. SP/AP ratios were elevated at day 2. The amplitude growth of the CAP did not differ between test and control groups at any time after implantation. EH can be suppressed by antagonism of mineralocorticoid receptors in the week after cochlear implantation. Reduction in EH did not lead to any change in hearing, and there was no indication of synaptopathy signalled by reduced CAP amplitude at high sound intensities. We found no electrophysiological evidence that EH early after implantation impacts negatively upon preservation of residual hearing.

Investigating the association of electrically-evoked compound action potential thresholds with inner-ear dimensions in pediatric cochlear implantation

ObjectivesA narrow bony cochlear nerve canal (BCNC), as well as a hypoplastic and aplastic cochlear nerve (CN) have been associated with increased electrically-evoked compound action potential (eCAP) thresholds in some studies, suggesting poorer neural excitability in cochlear implantation. Also, in large cochleae the extent of activated spiral ganglion neurons with electrical stimulation is less than in smaller ones. However, a detailed description of the relationship between eCAP thresholds for a lateral-wall electrode array and dimensions of the inner-ear structures and internal auditory canal (IAC) is missing. DesignThe study subjects were 52 pediatric patients with congenital severe-to-profound hearing loss (27 females and 25 males; ages 0.7–2.0 years; 1.0 ± 0.3 years, mean ± SD) implanted bilaterally with Cochlear Nucleus CI422, CI522, or CI622 implants with full insertion of the Slim Straight electrode array. Diameters of the cochlea and the BCNC as well as the widths and heights of the IAC and the CN were evaluated from preoperative computed tomography and magnetic resonance images. These anatomical dimensions were compared with each other and with the patients’ intraoperative eCAP thresholds. ResultsThe eCAP thresholds increased from the apical to basal direction (r = 0.89, p < 0.001). After sorting the cochleae into four size categories, higher eCAP thresholds were found in larger than in smaller cochleae (p < 0.001). With similar categorization, the eCAP thresholds were higher in cochleae with a larger BCNC than in cochleae with a smaller BCNC (p < 0.001). Neither IAC nor CN cross-sectional areas affected the eCAP thresholds. Correlations were found between cochlea and BCNC diameters and between IAC and CN cross-sectional areas (r = 0.39 and r = 0.48, respectively, p < 0.001 for both). ConclusionsIn the basal part of the electrode array, higher stimulation levels to elicit measurable neural responses (eCAP thresholds) were required than in the apical part. Increased eCAP thresholds associated with a larger cochlear diameter, but contrary to the earlier studies, not with a small size of the BCNC or the CN. Instead, the BCNC diameter correlated significantly with the cochlea diameter.

Comparisons of electrophysiological and psychophysical fitting methods for cochlear implants

Objective This study compared two different versions of an electrophysiology-based software-guided cochlear implant fitting method with a procedure employing standard clinical software. The two versions used electrically evoked compound action potential (ECAP) thresholds for either five or all twenty-two electrodes to determine sound processor stimulation level profiles. Objective and subjective performance results were compared between software-guided and clinical fittings. Design Prospective, double-blind, single-subject repeated-measures with permuted ABCA sequences. Study sample 48 post linguistically deafened adults with ≤15 years of severe-to-profound deafness who were newly unilaterally implanted with a Nucleus device. Results Speech recognition in noise and quiet was not significantly different between software- guided and standard methods, but there was a visit/learning-effect. However, the 5-electrode method gave scores on the SSQ speech subscale 0.5 points lower than the standard method. Clinicians judged usability for all methods as acceptable, as did subjects for comfort. Analysis of stimulation levels and ECAP thresholds suggested that the 5-electrode method could be refined. Conclusions Speech recognition was not inferior using either version of the electrophysiology-based software-guided fitting method compared with the standard method. Subject-reported speech perception was slightly inferior with the five-electrode method. Software-guided methods saved about 10 min of clinician’s time versus standard fittings.

Inner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss.

Age-related hearing loss in humans (presbycusis) typically involves impairment of high frequency sensitivity before becoming progressively more severe at lower frequencies. Pathologies initially affecting lower frequency regions of hearing are less common. Here we describe a progressive, predominantly low-frequency recessive hearing impairment in two mutant mouse lines carrying different mutant alleles of the Klhl18 gene: a spontaneous missense mutation (Klhl18lowf) and a targeted mutation (Klhl18tm1a(KOMP)Wtsi). Both males and females were studied, and the two mutant lines showed similar phenotypes. Threshold for auditory brainstem responses (ABR; a measure of auditory nerve and brainstem neural activity) were normal at 3 weeks old but showed progressive increases from 4 weeks onwards. In contrast, distortion product otoacoustic emission (DPOAE) sensitivity and amplitudes (a reflection of cochlear outer hair cell function) remained normal in mutants. Electrophysiological recordings from the round window of Klhl18lowf mutants at 6 weeks old revealed 1) raised compound action potential thresholds that were similar to ABR thresholds, 2) cochlear microphonic potentials that were normal compared with wildtype and heterozygous control mice and 3) summating potentials that were reduced in amplitude compared to control mice. Scanning electron microscopy showed that Klhl18lowf mutant mice had abnormally tapering of the tips of inner hair cell stereocilia in the apical half of the cochlea while their synapses appeared normal. These results suggest that Klhl18 is necessary to maintain inner hair cell stereocilia and normal inner hair cell function at low frequencies.

Noise-Induced Hearing Loss in Gerbil: Round Window Assays of Synapse Loss.

Previous work in animals with recovered hearing thresholds but permanent inner hair cell synapse loss after noise have suggested initial vulnerability of low spontaneous rate (SR) auditory nerve fibers (ANF). As these fibers have properties of response that facilitate robust sound coding in continuous noise backgrounds, their targeted loss would have important implications for function. To address the issue of relative ANF vulnerabilities after noise, we assessed cochlear physiologic and histologic consequences of temporary threshold shift-producing sound over-exposure in the gerbil, a species with well-characterized distributions of auditory neurons by SR category. The noise exposure targeted a cochlear region with distributed innervation (low-, medium- and high-SR neurons). It produced moderate elevations in outer hair cell-based distortion-product otoacoustic emission and whole nerve compound action potential thresholds in this region, with accompanying reductions in suprathreshold response amplitudes, quantified at 24 h. These parameters of response recovered well with post-exposure time. Chronic synapse loss was maximum in the frequency region initially targeted by the noise. Cochlear round window recorded mass potentials (spontaneous neural noise and sound-driven peri-stimulus time responses, PSTR) reflected parameters of the loss not detected by the conventional assays. Spontaneous activity was acutely reduced. Steady-state (PSTR plateau) activity was correlated with synapse loss in frequency regions with high concentrations of low-SR neurons, whereas the PSTR onset peak and spontaneous round window noise, both dominated by high-SR fiber activity, were relatively unaltered across frequency in chronic ears. Together, results suggest that acute targets of noise were of mixed SR subtypes, but chronic targets were predominantly low-SR neurons. PSTRs captured key properties of the auditory nerve response and vulnerability to injury that should yield important diagnostic information in hearing loss etiologies producing cochlear synaptic and neural loss.